109PD - Overall survival (OS) with afatinib (A) vs chemotherapy (CT) in patients (pts) with NSCLC harbouring EGFR mutations (mut): Subgroup analyses by race...

Date 16 April 2015
Event ELCC 2015
Session Advanced NSCLC
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Presenter Martin Schuler
Citation Annals of Oncology (2015) 26 (suppl_1): 29-44. 10.1093/annonc/mdv050
Authors M. Schuler1, J.C. Yang2, L.V. Sequist3, N. Yamamoto4, C. Zhou5, C. Hu6, K. O'Byrne7, V. Hirsh8, T.S.K. Mok9, Y. Wu10
  • 1West German Cancer Center, University Hospital Essen, University Duisburg-Essen, 45147 - Essen/DE
  • 2Department Of Oncology, National Taiwan University Hospital and National Taiwan University, Taipei/TW
  • 3Department Of Thoracic Oncology, Massachusetts General Hospital and Harvard Medical School, Boston/US
  • 4Third Department Of Internal Medicine, Wakayama Medical University, Wakayama/JP
  • 5Shanghai Pulmonary Hospital, Tongji University, Shanghai/CN
  • 6Xiangya Hospital, Central South University, Changsha/CN
  • 7Translational Research Institute, Princess Alexandra Hospital and Queensland University of Technology, Brisbane/AU
  • 8Department Of Oncology, McGill University, Montreal/CA
  • 9State Key Laboratory Of South China, Hong Kong Cancer Institute, The Chinese University of Hong Kong, Hong Kong/CN
  • 10Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou/CN



In the LL3 (345 pts recruited globally) and LL6 (364 Asian-only pts [no Japanese]) phase 3 randomised trials, first-line A, an irreversible ErbB family blocker, significantly improved OS vs cisplatin/pemetrexed (33.3 vs 21.1 months; HR 0.54; p = 0.0015) and gemcitabine/cisplatin (31.4 vs 18.4 months; HR 0.64; p = 0.023) in pts with advanced NSCLC harbouring EGFR Del19 mut; no significant difference in OS was observed in EGFR L858R mut-positive patients in either study.


In each study, pts were randomised (2:1) to 40 mg/day oral A or up to 6 cycles of CT, stratified by EGFR mut (Del19/L858R/other) and race (LL3 only; Asian/non-Asian). Pre-planned subgroup analyses of OS by race including Asian, non-Asian (LL3 only), and Japanese patients (LL3 only) are reported.


Significant improvements in OS in NSCLC pts harbouring EGFR Del19 mut were observed in all race subgroups analysed. In the Asian subgroup of LL3, median OS in Del19 pts (n = 123) was 33.3 months with A vs 22.9 months with CT (HR 0.57 [95% CI 0.36–0.90]; p = 0.015). In the non-Asian subgroup of LL3, median OS in Del19 pts (n = 46) was 33.6 months with A vs 20.0 months with CT (HR 0.45 [95% CI 0.21–0.95]; p = 0.03). In the Japanese subgroup of LL3, median OS in Del19 pts (n = 39) was 46.9 months with A vs 31.5 months with CT (HR 0.34 [95% CI 0.13–0.87]; p = 0.018). Significant improvement in OS with A vs CT was also observed in the combined analysis of Asian Del19 pts (n = 309) in LL3 and LL6 (median 31.7 vs 21.1 months; HR 0.61 [95% CI 0.46–0.82]; p = 0.001). No statistically significant difference in OS with A vs CT was observed for L858R mut pts in any of the race subgroups analysed.


Significant improvement in OS with first-line A vs CT in pts with NSCLC harbouring EGFR Del19 mut was demonstrated in subgroup analyses of Asian, non-Asian, and Japanese pts. These findings are consistent with analysis of the overall LL3 and LL6 pooled population.

Clinical trial identification EudraCT No. 2008-005615-18


M. Schuler: Prof. Schuler reports advisory board participation for, and corporate sponsored research from, Boehringer Ingelheim.

J.C.-H. Yang: Prof. Yang reports; advisory board participation for Boehringer Ingelheim, Pfizer, Novartis, AstraZeneca, Roche/Genentech, Clovis Oncology, MSD, Merck Serono and Eli Lilly; and corporate sponsored research from Boehringer Ingelheim.

L.V. Sequist: Dr Sequist reports non-compensated advisory board participation for Boehringer Ingelheim, AstraZeneca, Clovis, Novartis, Merrimack and Taiko.

N. Yamamoto: Dr Yamamoto reports advisory board participation for Boehringer Ingelheim.

C. Zhou: Prof. Zhou reports advisory board participation for Boehringer Ingelheim, Roche and Lily.

K. O'Byrne: Prof. O'Byrne reports advisory board participation for Boehringer Ingelheim.

V. Hirsh: Prof. Hirsh reports advisory board participation for Boehringer Ingelheim.

T.S.K. Mok: Ad board: AstraZeneca, Roche, Eli Lilly, Merck Serono, Eisai, BMS, AVEO, Pfizer, Taiho, Boehringer Ingelheim, Novartis, GSK Biologicals, Clovis Oncology, Amgen, Janssen, BioMarin; board of directors: IASLC; corporate-sponsored research: AstraZeneca

All other authors have declared no conflicts of interest.